Affiliation: University of California
Sharma K, Ramachandrarao S, Qiu G, Usui H, Zhu Y, Dunn S, et al
. Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest. 2008;118:1645-56 pubmed publisher
..These results suggest that adiponectin is a key regulator of albuminuria, likely acting through the AMPK pathway to modulate oxidant stress in podocytes. ..
Zhao J, Miyamoto S, You Y, Sharma K. AMP-activated protein kinase (AMPK) activation inhibits nuclear translocation of Smad4 in mesangial cells and diabetic kidneys. Am J Physiol Renal Physiol. 2015;308:F1167-77 pubmed publisher
..We conclude that stimulation of Smad4 in cell culture and in in vivo models of early diabetic kidney disease is dependent on AMPK. ..
You Y, Quach T, Saito R, Pham J, Sharma K. Metabolomics Reveals a Key Role for Fumarate in Mediating the Effects of NADPH Oxidase 4 in Diabetic Kidney Disease. J Am Soc Nephrol. 2016;27:466-81 pubmed publisher
..Fumarate is therefore a key link connecting metabolic pathways to DKD pathogenesis, and measuring urinary fumarate levels may have application for monitoring renal NOX4 activity. ..
Hallan S, Sharma K. The Role of Mitochondria in Diabetic Kidney Disease. Curr Diab Rep. 2016;16:61 pubmed publisher
..Furthermore, intermittent fasting and various pharmacological agents are other potential options for stimulating mitochondrial function and reducing the risk of development and progression of diabetic kidney disease. ..
Coughlan M, Sharma K. Challenging the dogma of mitochondrial reactive oxygen species overproduction in diabetic kidney disease. Kidney Int. 2016;90:272-279 pubmed publisher
..With improved tools and real-time imaging capacity, a greater understanding of the complex role of ROS will be able to guide novel therapeutic regimens. ..
Miyamoto S, Hsu C, Hamm G, Darshi M, Diamond Stanic M, Declèves A, et al
. Mass Spectrometry Imaging Reveals Elevated Glomerular ATP/AMP in Diabetes/obesity and Identifies Sphingomyelin as a Possible Mediator. EBioMedicine. 2016;7:121-34 pubmed publisher
..Our findings suggest that AMPK is reduced in the diabetic kidney due to an increase in the ATP/AMP ratio and that SM(d18:1/16:0) could be responsible for the enhanced ATP production via activation of the glycolytic pathway. ..
Sharma K. Mitochondrial hormesis and diabetic complications. Diabetes. 2015;64:663-72 pubmed publisher
BÃ¶rgeson E, Wallenius V, Syed G, Darshi M, Lantero Rodriguez J, BiÃ¶rserud C, et al
. AICAR ameliorates high-fat diet-associated pathophysiology in mouse and ex vivo models, independent of adiponectin. Diabetologia. 2017;60:729-739 pubmed publisher
..Furthermore, AICAR reduced inflammation in human adipose tissue explants, suggesting by proof-of-principle that the drug may reduce obesity-induced complications in humans. ClinicalTrials.gov NCT02322073. ..
Zhang G, Saito R, Sharma K. A metabolite-GWAS (mGWAS) approach to unveil chronic kidney disease progression. Kidney Int. 2017;91:1274-1276 pubmed publisher
..e., lysine and NG-monomethyl-l-arginine) with single-nucleotide polymorphisms of SLC7A9. ..